The focus of our research group is on autoimmune diseases, such as bullous pemphigoid, allergies, cancer and inflammatory skin diseases including atopic dermatitis, contact eczema and psoriasis. We are particularly interested in the role of basophils, eosinophils and mast cells in these diseases since the inflammatory mediators released from these cells play a crucial role in the severity of symptoms and also impact on other immune cells that govern these diseases. Our group has many years of experience in isolating and purifying human allergic effector cells in order to study their functional responses and shed light on the intracellular signaling mechanisms that control their reactivity. Our main goal is to understand the different roles these cells play in autoimmunity and allergies and in developing new therapeutic strategies.
Ongoing international research collaborations include the University of Groningen (NL), where we are researching the causes of skin blistering in bullous pemphigoid, Imperial College London (UK) and the University Clinic of Pulmonary and Allergic Diseases Golnik (SLO), where we are investigating the cellular causes for severe allergic reactions, and the University of Kent, where we are studying fundamental mechanisms responsible for autoimmune diseases and cancer.
Bullous pemphigoid (BP) is a blistering autoimmune dermatosis that belongs to the group of rare autoimmune diseases. The symptoms of bullous pemphigoid are initially described by itching with erythema and later blistering. Notably, bullous pemphigoid occurs in the elderly. The etiology of bullous pemphigoid is explained by the formation of IgG autoantibodies to hemidesmosomal antigens such as the bullous pemphigoid antigen 1 (BP230) and the bullous pemphigoid antigen 2 (BP180). BP180 is a transmembrane member of the collagen type XVII protein identified as the primary antigenic target of BP autoantibodies. BP180 is expressed on the basal surface of basal epidermal keratinocytes and is a member of the hemidesmosomal complex, a cellular structure that functions as a dermo-epidermal adhaesion. The major epitopes of BP180 associated with the disease are mapped to the NC16A domain. In addition to the IgG auto-AK also IgE AK play a pathogenetic role in bullous pemphigoid.
Characteristic of the bullous pemphigoid is a massive infiltrate of eosinophils. Blistering is caused not only by the binding of auto-AK, but also by the predominantly granulocytic infiltrate, complement and eosinophil proteases. In addition, the number of basophils in the dermis is increased in patients with bullous pemphigoid.
We are particularly interested in the role of basophils and eosinophils in bullous pemphigoid. The research is funded, inter alia, by the DFG. There is also a research cooperation with the working group of Prof. Marcel Jonkman from the UMCG Groningen, in which we jointly study the causes of blistering of the skin in the case of bullous pemphigoid as part of a Joint-Ph.D. program (Project 4: "Bullous pemphigoid - What makes the blister?").
Chronic pruritus ("chronic itching") is one of the most common symptoms of many skin conditions and can significantly worsen the quality of life. Chronic inflammatory skin diseases, including lichen planus (LP), psoriasis (PSO) and atopic dermatitis (AD), are a major cause of chronic pruritus. Nevertheless, these diseases are fundamentally different in terms of phenotype, histopathology and immunological principles underlying the course of the disease. There is increasing evidence that IL-17, IL-31, NGF and TSLP play a crucial role in pruritus. Therapeutic antibodies targeting either IL-17A or IL-31A have been shown to effectively reduce itching in PSO and AD, respectively. However, the molecular basis of chronic pruritus in dermatitis is still largely unexplained.
Our main goal is to characterize known (IL-31, NGF, TSLP) and to identify new pruritus signaling pathways in chronic dermatitis using transcriptome and cytokine analyzes of skin infiltrating T cells, mast cells and eosinophils and peripheral blood mononuclear cells (PBMCs) Open up therapy options.
Our group is part of the Translational Pruritus Research Group (Translational Pruritus Research, PruSearch FOR 2690), which is funded by the German Research Foundation (DFG). The research group consists of scientists and experts in the field of pruritus research in Germany with various specializations such as dermatology, neurophysiology, anesthesiology, neurology, gastroenterology and radiology.
Within the framework of this research group we identify and characterize together with the working group of Prof. Bernhard Homey of the UKD Dusseldorf the pruritus signaling pathways in chronic dermatitis (Projekt 5: Identifizierung und Charakterisierung von Pruritus Signalwegen bei chronischer Hautentzündung).
Negative immune checkpoint regulators attract continuous attention, as they are highly effective targets in the immunotherapy of malignant diseases. However, autoimmune reactions are common side effect of this treatment. A majority of patients treated with immune checkpoint inhibitors suffers from dermatological inflammatory disorders, including rash and pruritus, through to severe dermatologic manifestations, like lichenoid reactions, psoriasis, acneiform rashes, vitiligo-like lesions and autoimmune skin diseases. These observations clearly indicate a link between inflammatory skin diseases and immune regulation by immune checkpoints.
In this project we are aiming at understanding the molecular mechanisms that underlie immune checkpoint regulation. We anticipate that immune checkpoints play critical roles in inflammatory skin disease – beyond the well-established inhibition of T-cell functions. The project is partially funded by the intramural Funding of the School of Medicine and Healthcare Sciences, University of Oldenburg (Role of immune checkpoint regulators in inflammatory skin diseases, 2017-013).